(+/-)-N-trifluoroacetyl-1-[3,5-dimethoxy-4-(1-oxo-3-phenylpropy)phenyl]-2-aminopropane | 289889-81-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (+/-)-N-trifluoroacetyl-1-[3,5-dimethoxy-4-(1-oxo-3-phenylpropy)phenyl]-2-aminopropane
• 英文别名: N-[1-[3,5-dimethoxy-4-(3-phenylpropanoyl)phenyl]propan-2-yl]-2,2,2-trifluoroacetamide
• CAS: 289889-81-2
• 化学式: C₂₂H₂₄F₃NO₄
• 分子量: 423.432
• InChiKey: JXEQFYNYUNRYLN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (+/-)-N-trifluoroacetyl-1-[3,5-dimethoxy-4-(1-oxo-3-phenylpropy)phenyl]-2-aminopropane 在 palladium on activated charcoal sodium hydroxide 、 高氯酸 、 氢气 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 7.0h， 生成 2-[3,5-Dimethoxy-4-(3-phenyl-propyl)-phenyl]-1-methyl-ethylamine
  参考文献：
  名称：

  1-[4-(3-Phenylalkyl)phenyl]-2-aminopropanes as 5-HT_2A Partial Agonists

  摘要：

  Phenylalkylamines such as 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane (DOB; Pa) and its corresponding iodo derivative DOI (2) are commonly used 5-HT2 serotonin agonists. Previous studies have established that the 2,5-dimethoxy substitution pattern found in these compounds is optimal for high affinity at 5-HT2A receptors and that substituents at the 4-position can modulate affinity over a wide range. We have previously shown, however, that when the 4-position is substituted with a 3-phenylpropyl substituent (i.e., 3), the compound binds with an affinity comparable to that of Pa but that it possesses 5-HT2A antagonist character. The present study examined the structure-affinity relationships of 3, and the results were very much unexpected. That is, the 2,5-dimethoxy substitution pattern of 3 is not required for high affinity. Either of the two methoxy groups can be removed without untoward effect on affinity, and relocation of the methoxy substituents actually enhances affinity by as much as an order of magnitude. None of the compounds displayed more than 20-fold selectivity for 5-HT2A over 5-HT2C receptors. In addition, several were demonstrated to act as 5-HT2A partial agonists. As such, the results of this study suggest that the structure-affinity relationships of phenylalkylamines as 5-HT2A ligands now be reinvestigated in greater detail.

  DOI：

  10.1021/jm9906062
• 作为产物：
  描述：

  1-(3,5-dimethoxyphenyl)propan-2-amine 在 四氯化钛 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 生成 (+/-)-N-trifluoroacetyl-1-[3,5-dimethoxy-4-(1-oxo-3-phenylpropy)phenyl]-2-aminopropane
  参考文献：
  名称：

  1-[4-(3-Phenylalkyl)phenyl]-2-aminopropanes as 5-HT_2A Partial Agonists

  摘要：

  Phenylalkylamines such as 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane (DOB; Pa) and its corresponding iodo derivative DOI (2) are commonly used 5-HT2 serotonin agonists. Previous studies have established that the 2,5-dimethoxy substitution pattern found in these compounds is optimal for high affinity at 5-HT2A receptors and that substituents at the 4-position can modulate affinity over a wide range. We have previously shown, however, that when the 4-position is substituted with a 3-phenylpropyl substituent (i.e., 3), the compound binds with an affinity comparable to that of Pa but that it possesses 5-HT2A antagonist character. The present study examined the structure-affinity relationships of 3, and the results were very much unexpected. That is, the 2,5-dimethoxy substitution pattern of 3 is not required for high affinity. Either of the two methoxy groups can be removed without untoward effect on affinity, and relocation of the methoxy substituents actually enhances affinity by as much as an order of magnitude. None of the compounds displayed more than 20-fold selectivity for 5-HT2A over 5-HT2C receptors. In addition, several were demonstrated to act as 5-HT2A partial agonists. As such, the results of this study suggest that the structure-affinity relationships of phenylalkylamines as 5-HT2A ligands now be reinvestigated in greater detail.

  DOI：

  10.1021/jm9906062